The long-term objective of the research proposed here is to advance knowledge of the pathologic processes occurring in vitiligo, a disease in which pigment cells of the skin and eyes are destroyed. The experiments are aimed at analyzing the basis for depigmentation in two animal models for vitiligo: the extensively studied Smyth chicken (previously referred to as the DAM chicken) and a new mammalian, murine model (vi/vi). The two approaches to be taken concern the basic, melanocytic defect and the subsequent, autoimmune response. Both the pigmentary and the immune systems will have to be manipulated in concert during any therapeutic regimen that might be indicated by the results of the proposed research. The experiments include in-depth studies of melanization in the Smyth line, both within choroidal melanocytes and in neural-tube derived melanocytes that malfunction in culture in a manner similar to that observed in melanocytes in vivo. The causal relationship between aberrant melanization and the selective autophagocytosis of melanosomes will also be investigated. Serum from Smyth chickens obtained during various developmental stages of the vitiligo, will be screened for melanocyte-specific antibodies. Such antibodies will then be used to localize the melanocyte-specific antigens immunocytochemically by electron microscopy. A search for cutaneous versus choroidal melanocyte-specific surface antigens will be initiated by establishing pure cultures of the respective melanocyte types. In addition, morphologic analysis of hair bulb and eye depigmentation in the vi/vi mouse will be initiated as well as screening for anti-melanocyte factors in the serum of this prematurely graying mutant line.